Solid tumors exhibit the property of angiogenesis, i.e. the capacity to induce the proliferation of new capillary blood vessels from the host. The continued growth of a tumor appears to be bound to angiogenesis. It has been shown that angiogenesis is an early marker of pre-neoplastic lesions. Furthermore, we have shown that the angiogenesis capacity of the aqueous humor of human eyes could be used as a diagnostic marker for malignant eye lesions. We now propose to determine if the aqueous humor of patients with eye tumors will stimulate capillary endothelial migration in a significantly greater fashion than the aqueous humor of patients with non-malignant conditions. Such an assay might be used as a quantitative method for ocular malignancies. This will be done using capillary endothelial cells which we have recently isolated, cloned, and maintained in culture. The basis for this assay is that these capillary cells, unlike endothelial cells from the aorta or umbilical veins, will only grow and migrate in the presence of tumor-conditioned medium. Preliminary evidence has been obtained with shows that substances causing angiogenesis in vivo cause migration of capillary endothelial cells, but not other cell lines in vitro. We plan to measure the migration of capillary endothelial cells by means of a phagokinetic track assay of aqueous humor obtained from patients undergoing ophthalmologic surgery for both malignant and non-malignant eye lesions. We propose to test whether malignant lesions of the eye can be distinguished from non-malignant lesions based on the ability of the aqueous humor to stimulate the migration of capillary endothelial cells. In addition, we plan to determine to what extent capillary endothelial cell migration in vitro correlates with angiogenesis in vivo. Finally, we will investigate the possibility of using this diagnostic method to detect patients at high risk to develop malignant eye lesions such as siblings of patients with retinoblastoma.